Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by the ectopic expression of defined factors. iPSCs hold great promise for pharmaceutical screening and regenerative medicine but the mechanism of reprogramming is not well understood. This work examines a component process of reprogramming that is the mesenchymal-to-epithelial transition (MET), an important step in the generation of iPS cells. In this thesis I demonstrate a connection between BMP signaling and the reprogramming factor Klf4 in the activation of the MET expression program. Using ChIP-Seq I mapped the binding of Klf4 and BMP Smads across the genome and linked their co-binding to a MET expression program determined by RNA-Seq. My work uncovers a thus-far unreported interaction between Klf4 and BMP signaling in cellular epithelialization that can directly improve the technical methods of reprogramming and have important implications for the induction of epithelial tissues in general.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/44038 |
| Date | 18 March 2014 |
| Creators | Liu, Da |
| Contributors | Wrana, Jeffrey |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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